ACUTE RHEUMATIC FEVER AND

RHD

By. Admas G.
(MD, INTERNIST)
Outline

1. Introduction
2. Etiology and pathogenesis
3. Clinical Features and Laboratory findings in ARF
4. Diagnosis of ARF
5. Management and Prevention of ARF
6. Summary
 Introduction
• ARF is a post infectious, non-suppurative sequel of
pharyngeal infection with Streptococcus pyogenes
• RHD is the only long-term sequel of ARF
• RHD manifests after several years of ARF with heart
failure or complications like stroke or IE.
• ARF and RHD can easily be prevented by early
identification and treatment of streptococcal
pharyngeal infection.
Epidemiology of RHD
• Currently affects over 33 million people worldwide
• Found all over the world
– most commonly affects women, adolescents and children
living in conditions of poverty and overcrowding.
• RHD kills 275,000 people every year. (preventable
disease?)
• A few rich countries (including the USA and UK) and
some LMIC Countries like Cuba have managed to reduce
their burden of RHD, but other countries continue to
struggle with the disease.
• A lifelong condition, which is often fatal if not treated
properly
 RHD in Ethiopia
• Recent school and community based studies in Ethiopia
have shown the prevalence of RHD in 4-24 years age
groups to be from 14-38/1000,which is one highest in
the world.
• Approximately 250, 000 people in the age group 5-15
suffer from RHD in Ethiopia.
• More than 500,000 people of all age groups live with
RHD.
• Only few give history of Acute Rheumatic Fever
 RHD in Ethiopia…
• RHD is the main cardiovascular diagnosis
accounting for 30-60% of all cardiac patients in
main hospitals of Ethiopia
• Patients usually come late with heart failure , stroke
or during pregnancy with severe valvular disease
• Mortality from RHD may reach up to 12.5% every year
in rural Ethiopia.
• It is also reported that 70% of RHD patients die before
the age of 26 years.
 Risk Factors for
•
Rheumatic Fever
Socioeconomic status:
– Poverty
– Poorly made and overcrowded housing
– Lack of adequate health care
– Untreated GAS infections
• Sex
• RF occurs in equal numbers in males and females, but the prognosis is
worse for females than for males.
• Age
– RF principally affects children between 5-15 years of age
with a median age of 10 years, although it also occurs in
adults (20% of cases).
• Risk factor for RHD
– Recurrent ARF
 Risk factors for Rheumatic Fever
Determinants Effects Impact on ARF and RHD
burden
Socioeconomic & environmental
factors
1. Rapid spread of 1. Higher incidence of acute strep
1. Poverty GABHS pharyngitis and complications
2. Poor nutrition 2. Difficulties accessing 2. Higher incidence of ARF and
health care recurrent ARF
3. Overcrowding
4. Poor standard of living
Health System Related Factors 1. Higher incidence of ARF and
recurrent ARF
1. Shortage of resources for 1. Inadequate diagnosis
health care and treatment of strep 2. Missed first ARF episode
pharyngitis
2. Low level of knowledge of 3. Inadequate secondary prophylaxis
disease among health care 2. Misdiagnosis or late delivery
providers diagnosis of ARF
4. Higher rates of recurrent ARF with
3. Low level of awareness of 3. Inadequate secondary more frequent and severe heart valve
disease in the community prophylaxis delivery involvement
5. Higher rates of repeated hospital
admissions and expensive heart
valve surgery
 Etiology and Pathogenesis
• Rheumatic fever is thought to result from an
inflammatory autoimmune response with antibodies
produced against streptococcal antigen induces
inflammation in host tissue having similar molecules
(ANTIGEN MIMICKERY THEORY)
• Only group A beta-hemolytic streptococcal infections
of the pharynx initiate or reactivate rheumatic fever.
• In 0.3-3% of streptococcal pharyngeal infection,
rheumatic fever develops several weeks after the sore
throat has resolved.
• Studies show the existence of genetic predisposition in
addition to bacterial factors.
 Etiology and Pathogenesis…
• After recovery from the initial episode of RF, up to
60% to 65% of patients develop valvular heart
disease and the risk of RF recurrence following GAS
infection rises to 50%.
• Repeated GAS infections without appropriate
treatment leads to RF recurrences and progressive
valve damage-the defining characteristic of RHD
which can, in turn, cause atrial fibrillation, heart
failure, stroke and endocarditis.
Cascade of RF and RHD
 Clinical Features
• Following sore throat with GABHS:
– Silent period of 2 - 6 weeks
– Sudden onset of fever, pallor, malaise, fatigue
• After which characteristic manifestations rheumatic fever start to
appear:
– Arthritis
– Carditis
– Erythema marginatum
– Subcutaneous nodules
– Sydenham’s chorea
• In one third of patients the streptococcal infection passes
unnoticed and 54 to 70% of recurrences of ARF were caused by
asymptomatic streptococcal infection.
Clinical Manifestations
 1. Arthritis
• It occurs in about 75% of cases.
• Usually a polyarthritis involving big joints: knees,
ankles, elbows, wrists
• Asymmetrical
• Migratory (fleeting)
• Joints are hot, red, tender, swollen with limited
mobility
• It is unusual to involve the central joints as spines,
hips and the peripheral ones as the fingers and toes.
Infrequently it involves the tempromandibular joint.
 Arthritis…
• No residual deformity (licks)
• It is more common and more severe in
teenagers and young adults than in children
• Lasts 2-6 weeks
• Dramatic response to salicylates
 2. Carditis
• Occurs in 40% of patients during the first attack
and almost 100% if ARF recurs.
• It may be the only major manifestations and usually
appears in the first week of the illness.
• May lead to death in acute phase or at later stage
• Any cardiac tissue may be affected (Pancarditis)
• Valvular lesion most common: mitral and aortic
• Seldom see isolated pericarditis or myocarditis
 Carditis….
Pancarditis is the most serious and second most
common complication of rheumatic fever (50%).
In advanced cases, patients may complain of dyspnea,
mild-to-moderate chest discomfort, pleuritic chest
pain, edema, cough, or orthopnea if they develop
congestive heart failure and pericarditis.
Upon physical examination, carditis is most
commonly detected by a new murmur and
tachycardia out of proportion to fever.
The murmurs of acute ARF are typically due to valve
insufficiency.
…
• Clinical signs:
 High pulse rate
 Murmurs : Mitral and aortic regurgitation most
common
 Pericarditis usually asymptomatic
 Occasionally causes chest pain, friction rubs or distant
heart sounds
 Cardiomegaly
 Rhythm disturbances (prolonged PR interval)
 Heart failure
Clinical Features of Carditis
3. Sydenham’s Chorea(10-20%)
• Occurs in 10-20% of rheumatic fever patients
– Due to basal ganglia involvement
• May be associated with normal laboratory findings
• Involuntary, sudden, semi-purposeful movements of
limbs face and tongue. Disappear during sleep
• Hypotonia and hyporeflexia
• Emotional labiality and instability
• More in females
• Latent period (2-6 months). No arthritis and ESR is
usually normal
• Self-limiting
Chorea..
 4. Subcutaneous Nodule
– Small, painless, firm, mobile
– Accumulated Aschoff nodules.
– Over bony prominences, tendons .
– Often associated with severe
carditis.
– Can occur with other diseases like
rheumatoid arthritis
– They last for a week or two and
rarely more than a month, and
sometimes disappear within several
days.
5. Erythemia Marginatum (10%)
– Erythema with central pallor.
– More on trunk and proximal limbs.
– It usually occurs in the covered
parts and may be manifested by
local application of heat.
– Nonpruritic, nonpainful.
– Often associated with acute
carditis.
– They disappear within hours and
may appear intermittently within
weeks to months
 Laboratory findings in ARF
1. Elevated acute phase reactants
1. Erythrocyte sedimentation rate(>30mm/hr)
2. Leukocytosis
3. C-reactive protein
2. Recent Evidence of Group A Streptococcal infection :
– Raised ASO titer (80% of cases)
– Anti DNAase B
– Antihyaluronidase
– Rapid Stretococcal antigen test.
– Positive throat culture for (GAS),
– Recent scarlet fever (fever, exudative pharyngitis and
exanthem )
3. Increased PR interval on EKG (first degree heart block )
 Imaging
• Cardiomegaly and signs of Heart failure on
Chest x-ray
• 2D and Doppler Echocardiography
– To identify and assess severity of carditis
 Diagnosis of ARF
• No specific laboratory test to diagnose ARF
• Diagnosis is based on clinical criteria.

The 2015 ACC/AHA ARF Revised Jones criteria

Plus
evidence of recent streptoccal infection
 Revised Jone’s Criteria for Diagnosis of ARF (2015 ACC/AHA )

Evidence of preceding group A streptococcal infection (other than chorea):

 Raised ASO titer ,OR
 Positive throat culture for GABH,OR
 Positive Rapid antigen test, OR
 Clinical evidence of bacterial Tonsilo-pharyngitis

Diagnosis : Initial ARF 2 major or 1 major plus 2 minor manifestations PLUS evidence of
recent strep infection (other than chorea)
2 major or 1 major and 2 minor or 3 minor PLUS evidence of
Recurrent ARF recent strep infection(other than chorea)
Criteria
A. Major B. Minor
 Arthritis (Monoarthritis or polyarthritis  Monoarthralgia
or polyarthralgia)a
 Carditisb (Clinical and/or subclinical)  Fever (≥38°C)
 Chorea  ESR ≥30 mm/h and/or CRP ≥3 mg/dLc
 Erythema marginatum  Prolonged PR on ECG (for age) (unless carditis is a
major criterion
 Subcutaneous nodules
 Diagnostic Classes of New ARF
Definite ARF:
 2 major, or 1 major plus 2 minor manifestations PLUS
evidence of recent strep infection (other than chorea)
Highly Probable ARF:
 If an ARF diagnosis is considered highly probable (but
not confirmed due to lack of evidence for recent
streptococcal infection)
Uncertain ARF:
 In patients from high-risk groups with only one major
manifestation of acute Rheumatic fever or borderline
echocardiographic findings .
 Treatment for ARF
• Admission to hospital
– Admit all patients suspected to have ARF
• Confirmation of the diagnosis:
– Observation prior to anti-inflammatory
treatment: paracetamol may be given for
fever or joint pain
– Investigations: CBC,ESR,CXR,ECG,
Echocardiography
 …
1. Treat Infection: Antibiotics: :
o A single intramuscular injection of benzathine
penicillin G (BPG) to eradicate GAS from upper
respiratory tract.
600 000 IU for those less than 7 years and
1.2 million IU for those who are 7 years of age or more.
o After this initial course of antibiotic therapy the
patient should be started on long term monthly BPG
secondary prophylaxis.
o Oral erythromycin if allergic to penicillin
 …
2. Arthritis and fever
o Paracetamol until diagnosis is confirmed
o Mild arthralgia and fever may respond to paracetamol alone.
o Arthritis or Severe arthralgia :Aspirin, naproxen or ibuprofen once diagnosis is
confirmed, if present
 Start Aspirin 75 mg per kilogram per day divided 6 hourly after meals for 4
weeks , OR
 Ibuprofen 30mg/kg per day 8 hourly.
 Do ESR 2 weekly, taper aspirin by decreasing the dose by 2 tablets every week
o Patients not responding or not tolerating aspirin:
 start Prednisolone 2mg per kilogram per day for 2 weeks; then aspirin is added
at dose 60 mg per kilogram per day divided into 4 doses for another 2 weeks;
then Prednisolone is tapered & discontinued.
 Do ESR 2 weekly, taper aspirin by decreasing the dose by 2 tablets every
week.
…
3. Carditis/heart failure
• Bed rest, with mobilization as symptoms permit
• Urgent echocardiography
• Management of Heart Failure:
– Fluid restriction for mild or moderate failure
– Furosemide 1-2mg/kg PO per day
– ACE inhibitors for more severe failure, particularly if AR
present
– Digoxin and anticoagulants, if AF present
– Prednisolone can be given for severe carditis
– Valve surgery for life-threatening acute carditis(rare)
…
4. Chorea
– No treatment for most cases.
– Carbamazepine or valproic acid if treatment necessary
(for severe cases)
5. Other management considerations
– Register patient in a RHD Register
– Ask about family members: those with sore throat are
given one injection of benzathine penicillin or oral
antibiotics for 10 days.
– Educate client and family on dental care and
importance of secondary prophylaxis
Management of Probable ARF
A. Highly-Probable ARF:
 manage as for definite ARF
B. Uncertain ARF:
 Administer 12 months of secondary prophylaxis initially, and reassess
(including echocardiography) at 1 year.
 If there is no evidence of recurrent ARF, and no evidence of cardiac
valvular damage on echocardiography at 12 months, consider ceasing
secondary prophylaxis.
 Prevention of ARF:
Depends on eradication of group A streptococci from upper respiratory tract. It is
divided into:
1. Primordial Prevention:
• Improving socioeconomic conditions, nutrition, housing conditions (decreasing
crowding) and improving access to health care can all decrease the incidence of
ARF.
2. Primary prevention:
• Prompt treatment of GAS pharyngitis with one injection of IM BPG is highly
effective in preventing first attacks of ARF.
• However, about 1/3 of patients with ARF do not recall preceding episode of
pharyngitis
• A vaccine for GAS is being developed but has not yet been used in clinical
practice
3. Secondary Prophylaxis
• Monthly injection of BPG IM to prevent recurrences of rheumatic fever
• Community and combined school and
community sore throat treatment interventions
could be expected to reduce the incidence of
ARF by up to 60%.
• GAS pharyngitis is droplet-spread and the rate
of GAS pharyngitis cross-infection within a
household is between 19-50%.So household
contact tracing to interrupt the spread of GAS
following a case of rheumatic fever
SECONDARY PROPHYLAXIS IN
RHEUMATIC FEVER AND RHD
Definition
• Secondary prevention refers to the early detection of
disease and implementation of measures to prevent
recurrence and worsening disease

• Term used to describe regular delivery of antibiotics

to prevent recurrence of GAS infection and
subsequent development of ARF
 Indication for secondary prophylaxis

1. ARF confirmed by the Revised Jones Criteria

2. RHD confirmed on echocardiogram
3. ARF or RHD not confirmed but considered highly
‘probable’
4. RHD post-surgery

 NB: Continue prophylaxis in pregnant patients and

those on warfarin.
Benefits of Secondary prevention in RF/RHD

• Prevent further GAS infections

• Prevent recurrence ARF
• Prevent the development of RHD
• Reduce the severity or worsening of RHD

o It is associated with regression of heart disease in

approximately 50-70% of those with good adherence
over a decade and reduces mortality
Standard Drugs for secondary prophylaxis

A. Benzathine Penicillin G
 is the most effective method of secondary
prophylaxis
 given by deep intramuscular injection every 4
weeks.
 The standard dose is:
 1,200,000 units for ALL people >30kg
 600,000 units for children <30kg
…
B. Erythromycin
 given if there is a proven allergy to Penicillin
 The standard dose is
 250mg oral, twice-daily for children < 7 yrs and
 500mg PO BID for ALL people > 7 years of age

 Antibiotics need to be present in the body at all times

to effectively prevent GABHS infections which can
result in recurrent ARF.
Benzathine Penicillin G use recommendations

I. Benzathine Penicillin G (BPG) is an essential medicine for

treatment and for prevention of ARF/RHD
II. Alternatives to BPG (e.g. oral medicines) are not as effective
as BPG
III. Serious allergic reactions to BPG are rare and should not stop
us from using BPG.
IV. BPG injection can be given by any trained health worker
following standard procedures as shown below.
V. Skin testing with dilute BPG will not predict the patients who
are allergic, therefore it is not indicated.
VI. Inform patient or guardian and obtain informed verbal consent
STEP 2: Prepare the items needed

1. One 10 ml syringe
2. One 5 ml syringe
3. One BPG ampoule 1.2
million units
4. One vial of local anesthetic
lidocaine 2% (or water for
injection)
5. One adrenaline vial 1:1000
6. One antihistamine vial:
7. Promethazine 50mg inj
8. Normal saline 1000ml: 1
bag (with IV Cannula)
STEP 3: Prepare the injection

i. Draw appropriate amount of local anesthetic as

diluents for the BPG powder or water for
injection if no lidocaine(make sure it’s not cold)
ii. Inject the diluents into the BPG vial
iii. Mix gently till dissolved by rolling in the
hands
iv. Draw in 5 ml syringe
v. Change the needle to a large bore (10 ml
syringe) needle
STEP 4: Prepare the Patient and Give the Injection

1. Ask the patient to lie on the abdomen

2. Mark the site of the injection on the gluteus muscle
3. To minimize pain: press with your thumb over the site for 10
seconds
4. Aspirate first to avoid veins then give the injection SLOWLY
deep in the muscle.
5. Use new needle for each patient
6. Discard used needles and syringes in safety box
7. Keep the patient for 15 minutes
8. Document the date and dose on the patient chart and the
patient passport
• NEVER EVER GIVE BPG
INTRAVENOUSLY AS THIS MAY LEAD
TO IMMEDIATE DEATH!!

• SKIN TESTING IS NOT

RECOMMENDED TO CHECK FOR
ALLERGY TO BPG.
STEP 5: Observe and treat reactions

• Observe the patient for at least 15 minutes

 Classify reaction
A. Mild Reaction (Local Reaction) :
Itching, hives or urticaria: manage with antihistamine
injection. Continue observation until the patient is well
B. Severe Reaction (Anaphylaxis):
sudden face/tongue swelling with difficulty breathing, BP <
90/60 or collapses over minutes to hours
C. Vasovagal (Pain) Reaction:
 Sudden immediate collapse and transient loss of
consciousness usually in a very sick patient.
Prevalence of Penicillin Reactions
Potential barriers to BPG Use and suggested solutions
Management of Penicillin reaction

• Vasovagal Reaction
– is a transient loss of consciousness due to a reflex
response that encompasses vasodilatation and/or
bradycardia, leading to systemic hypotension and
cerebral hypoperfusion.
– occur due to pain of injection or emotional stress.
– It occurs more in patients with severe RHD.
Prevention of Vasovagal Reactions
• Use a smaller-gauge needle: a 21-gauge needle
• Warm syringe to room temperature immediately before using.
• Ensure that skin swabbed with alcohol is dry before injecting
• Apply gentle pressure to the injection site for 10 seconds with
the finger or thumb before injection
• Deliver injection slowly (preferably over at least 2–3 min)
• Distract patient during injection (e.g. with conversation)
• The addition of 0.5–1 mL of 1% lignocaine may help •
• Keep the patient supine during the injection
Management of Vasovagal reaction

• Protect patient from falls and injuries.

• Advised Pt to assume the supine position with legs
raised
• Advise the patient to do Isometric Counter-pressure
maneuvers :
 Leg-crossing with simultaneous tensing of leg, abdominal, and
buttock muscles –
Handgrip
 Arm tensing
• Educate and reassure the patient and family.
• Closely monitor vital signs
Anaphylaxis
Duration of Secondary Prophylaxis
Diagnosis & Management of RHD

By. Dr. Admas G.

(MD, INTERNIST)
Introduction

• RHD is inflammation of heart valves that

follows infection with GABHS, commonly
pharyngitis.
• RHD is the only long-term sequelae of ARF
which can lead to disability or death.
• 40-60% of patients with ARF will go on to
develope RHD.
• Rheumatic carditis affects mainly the heart
valves.
Epidemiology

• Unlike developed nations where RHD has

been virtually eliminated, it remains an
important public health problem in sub-
Saharan Africa (SSA) including Ethiopia.
• One community-based study on a
predominantly rural population in Ethiopia
revealed a prevalence of 37.5 definite cases
per 1000 population
…
• RHD was the major cause of cardiovascular morbidity
(in 46.6% of cases) among admitted patients and those
under follow-up in tertiary facilities in Ethiopia.
• Patients with symptomatic RHD face a very high
mortality rate.
• The 2010-2012 Global Registry of RHD (REMEDY
Study), of which Ethiopia was also a part, showed that
RHD patients were young, predominantly female, and
had high prevalence of major cardiovascular
complications.
Pathophysiology of RHD

• In most patients RHD remains clinically silent (10- 20

years) during which the valve lesion progresses to
cause significant valvular abnormalities due to
recurrent attacks of unrecognized Acute Rheumatic
Fever.
• History of Rheumatic fever can be elicited in less than
half of patients who come for the first time with RHD.
• Involvement of the valves is the fundamental
pathophysiologic change of RHD which affects mainly
the MITRAL and AORTIC valves.
…
• In patients with RHD permanent damage of
the valve apparatus leads to scarring resulting
in poor opening and closure of the valves.
• Patients can have isolated stenosis or
regurgitation or combined stenosis and
regurgitation.
• The mitral valve is the most common valve
involved followed by aortic, tricuspid and very
rarely pulmonary valve in that order.
Clinical Manifestations of RHD
• Symptoms of RHD may not develop for many
years
– A murmur but no symptoms usually suggests
mild-moderate disease
– Symptoms usually suggest moderate-severe
disease
Diagnosis of RHD
• Accurate diagnosis of RHD requires
echocardiographic detection of valve abnormality
and hemodynamic changes like regurgitation and
ejection fraction.

• Unfortunately, echocardiography is not available

widely and clinical suspicion is therefore very
important to early diagnose and prevent the
progression of RHD
…
• In general, all patients having HF symptoms or
manifestations which look like complications of
RHD should be referred to the next level of health
care for better diagnosis and/or echocardiographic
assessment by more qualified health professionals
(cardiologist, Internist or pediatrician).
 The first step is to make sure that there is no
rheumatic fever recurrence or infective
endocarditis.
Laboratory and other Investigations in RHD

 CBC and ESR

 Electrocardiogram (ECG)
• To check for rate and rhythm
 Chest X-ray (CXR)
• To determine size and placement of heart
• To look for signs of heart failure (pulmonary congestion)
 Echocardiography
 To identify heart valve damage
To estimate severity of disease
Useful to compare results with future echocardiogram results
Management of RHD

• The management of RHD is complex and

requires careful co-ordination.

• The main goal is to prevent disease

progression and to avoid, or at least delay,
valve surgery
Management principles
Effective baseline assessment, education and referral
• Establishing the diagnosis of RHD
• Detecting and treating Complications of RHD

Treatment of cardiac and other symptoms

Long-term secondary prophylaxis (to prevent recurrent ARF)

Regular medical and cardiology review including echocardiography

Appropriate and timely surgical interventions

Dental assessment and care

Advise on Family planning and referral

Management of RHD in special situations(e.g . pregnancy)

Common complication of RHD
Management of Heart Failure
Management of Atrial Fibrillation
• Most common arrhythmia is atrial fibrillation
– An irregularly irregular pulse
– commonly seen in patients with mitral stenosis
– most feared complication of atrial fibrillation is the
development of cardiac thromboembolism , resulting
in stork , PAD ….

 Patients having irregular heart rhythm should be

referred to hospitals to confirm the diagnosis and
initiate treatment for AF and anticoagulation
Infective Endocarditis

• Is infection of the damaged valves by

microbial agents which have got access to the
blood stream In RHD
• Endocarditis most commonly occurs in the
mitral or aortic valves
• Diagnostic Clues:
– Fever, hematuria, night sweating,weight loss,
clubbing, changing murmur, unexplained rapid
deterioration of heart failure, splenomegaly
…
Choice of Antibiotics
• After taking blood culture, the patient should be
started on IV antibiotics:
– Crystalline penicillin 3millin Units IV 4 hourly, OR
Ampicillin 2 g IV 4 hourly for 4-6 weeks.
– plus gentamicin 1mg/kg IV tid for 2 weeks.
– Ceftriaxone 2g IV/day can be used in place of
penicillin but it doesn’t cover enterococci.
– In case of prosthetic valve endocarditis, the drugs
should include vancomycin (15mg/kg BID IV)
Valve surgery or interventions for RHD

• The need for surgery and cardiac interventions in

RHD depends on:

Severity of symptoms
 Evidence that the heart valves are severely
damaged
 Left ventricular chamber size and ejection fraction
 Availability of long-term management after
surgery (i.e. anticoagulation)
Thank you